Recent structural characterizations of the p51 and p66 monomers has established an important starting point for understanding the maturation pathway of the HIV-1 reverse transcriptase p66/p51 heterodimer. This process requires a metamorphic transition of the polymerase domain leading to formation of a p66/p66' homodimer that exists as a structural heterodimer. In order to better understand the drivers for this metamorphic transition, we have performed NMR studies of (15)N-labeled RT216 - a construct that includes the fingers and most of the palm domains...

Functional materials that exhibit photoinduced structural phase transitions are highly interesting for applications in optomechanics and mechanochemistry. It is, however, still not fully understood how photochemical reactions, which are often accompanied by molecular motion, proceed in confined and crystalline environments. Here we show that thin films of azobenzene trimers exhibit high structural order and determine the crystallographic unit cell. We demonstrate that the thin film can be switched partially reversibly between a crystalline and an amorphous phase...

Bismuth sodium titanate, Bi0.5Na0.5TiO3 (BNT), is a promising lead-free ferroelectric material. However, its potential applications have not been fully explored, mainly because of the complex domain structure arising from its intricate phase transitions. A deep and thorough study of its domain structure and polarization switching behavior will greatly help with understanding the polarization nature and with promoting future applications. In this work, we demonstrate that BNT polycrystalline films possess a highly ordered out-of-plane polarization (self-polarization) and randomly oriented in-plane polarizations...

Importance: Knowing the range of symptoms seen in patients with a missense or loss-of-function variant in KCNB1 and how these symptoms correlate with the type of variant will help clinicians with diagnosis and prognosis when treating new patients. Objectives: To investigate the clinical spectrum associated with KCNB1 variants and the genotype-phenotype correlations. Design, Setting, and Participants: This study summarized the clinical and genetic information of patients with a presumed pathogenic variant in KCNB1...

BACKGROUND: Niemann-Pick disease, type C1 (NPC1) is a lysosomal storage disorder characterised by progressive neurodegeneration. In preclinical testing, 2-hydroxypropyl-β-cyclodextrins (HPβCD) significantly delayed cerebellar Purkinje cell loss, slowed progression of neurological manifestations, and increased lifespan in mouse and cat models of NPC1. The aim of this study was to assess the safety and efficacy of lumbar intrathecal HPβCD. METHODS: In this open-label, dose-escalation phase 1-2a study, we gave monthly intrathecal HPβCD to participants with NPC1 with neurological manifestation at the National Institutes of Health (NIH), Bethesda, MD, USA...

The comprehensive evaluation of nonmotor symptoms (NMS) in Parkinson's disease (PD) starts with the awareness of physicians, patients, and caregivers on their nature, clinical presentation, and effect on patient's daily activities and quality of life. This awareness can be better achieved if the symptoms can be visualized, measured, and monitored. As NMS are largely subjective in nature, a majority of them cannot be visualized (unlike tremor, which is easily seen), making their identification and quantification difficult...

My father was diagnosed with stomach cancer recently. Luckily, it was still at an early stage, and endoscopic surgery successfully took care of it. My father was fortunate; since people with stomach cancer do not show clear symptoms in the early stages, the disease is often not diagnosed until it becomes advanced. In his case, the diagnosis started from a suggestion by his doctor to check whether he had a gastric infection with Helicobacter pylori, a bacterial species found in the digestive tract. In Japan, where he lives, a majority of gastric cancer patients (more than 99%) have been infected with H...

BACKGROUND: Heterogeneity in patients with low back pain is well recognised and different approaches to subgrouping have been proposed. One statistical technique that is increasingly being used is Latent Class Analysis as it performs subgrouping based on pattern recognition with high accuracy. Previously, we developed two novel suggestions for subgrouping patients with low back pain based on Latent Class Analysis of patient baseline characteristics (patient history and physical examination), which resulted in 7 subgroups when using a single-stage analysis, and 9 subgroups when using a two-stage approach...

Cyclic GMP analogs, 8-Br, 8-pCPT, and PET-cGMP, have been widely used for characterizing cellular functions of cGMP dependent protein kinase (PKG) I and II isotypes. However, interpreting results obtained using these analogs has been difficult due to their low isotype specificity. Additionally each isotype has two binding sites with different cGMP affinities and analog selectivities, making understanding the molecular basis for isotype specificity of these compounds even more challenging. To determine isotype specificity of cGMP analogs and their structural basis, we generated the full-length regulatory domains of PKG I and II isotypes with each binding site disabled, determined their affinities for these analogs, and obtain co-crystal structures of both isotypes bound with cGMP analogs...

Objective: Assess the effect of a Health Education (HE) program on cognition, mood and functional capacity of participants in a University of The Third Age (U3A). Method: Controlled clinical trial. The HE Program consisted of 10 sessions with group dynamics, including orientations on disease prevention and cognitive stimulation exercises, lasting four months. Intervention Group (IG) n=13; and Control Group (CG) n=15. All were assessed at the start and end of the study, using Addenbrook´s Cognitive Examination-Revised (ACE-R), Beck Depression and Anxiety Inventory (BDI/BAI) and Functional Independence Measure (FIM)...

OBJECTIVE: The electromyographic bridge (EMGB) detects surface electromyographic signals from a non-paretic limb. It then generates electric pulse trains according to the electromyographic time domain features, which can be used to stimulate a paralysed or paretic limb in real time. This strategy can be used for the contralateral control of neuromuscular electrical stimulation (NMES) to improve motor function after stroke. The aim of this study was to compare the treat-ment effects of EMGB vs cyclic NMES on wrist and finger impairments in subacute stroke patients...

A 73-year-old woman diagnosed with unresectable pancreatic cancer received weekly gemcitabine(GEM)plus albuminbound paclitaxel(nab-PTX)therapy. Four months after nab-PTX therapy was initiated, she presented with a rapidly decreasing vision in her left eye at an ophthalmology clinic. On admission, her visual acuity was decreased, and optical coherence tomography(OCT)revealed a cystoid macular edema(CME)only in her left eye. She discontinued the nab-PTX therapy immediately. Her visual acuity improved on follow-up 6 months later...

In this review, we discuss the conditions for forming microemulsions, systems which are thermodynamically stable mixtures of oil and water made stable by the presence of an interfacial film containing surface active molecules. There are several types of microemulsions, depending largely on the stiffness of the amphiphilic monolayer that separates the oily and the aqueous micro-domain. We first discuss and compare the phase behaviour of these different types, starting from the classical microemulsion made from a flexible surfactant film but then also moving on to less classical situations: this occurs when the interfacial film is stiff or when microemulsions are formed in the absence of a classical surfactant...

The Archaea occupy a key position in the Tree of Life, and are a major fraction of microbial diversity. Abundant in soils, ocean sediments and the water column, they have crucial roles in processes mediating global carbon and nutrient fluxes. Moreover, they represent an important component of the human microbiome, where their role in health and disease is still unclear. The development of culture-independent sequencing techniques has provided unprecedented access to genomic data from a large number of so far inaccessible archaeal lineages...

MCR-2 confers resistance to colistin, a `last-line' antibiotic against extensively resistant Gram-negative pathogens. It is a plasmid-encoded phosphoethanolamine transferase that is closely related to MCR-1. To understand the diversity in the MCR family, the 1.12 Å resolution crystal structure of the catalytic domain of MCR-2 was determined. Variable amino acids are located distant from both the di-zinc active site and the membrane-proximal face. The exceptionally high resolution will provide an accurate starting model for further mechanistic studies...

We report the fully-scalable fabrication of a large array of hybrid molybdenum disulfide (MoS2) - silicon dioxide (SiO2) one-dimensional, free-standing photonic-crystal cavities capable of enhancement of the MoS2 photoluminescence at the narrow cavity resonance. We demonstrate continuous tunability of the cavity resonance wavelength across the entire emission band of MoS2 simply by variation of the photonic crystal periodicity. Device fabrication started by substrate-scale growth of MoS2 using chemical vapor deposition (CVD) on non-birefringent thermal oxide on a silicon wafer; it was followed by lithographic fabrication of a photonic crystal nanocavity array on the same substrate at more than 50% yield of functional devices...

DMRT genes encode a deeply conserved family of transcription factors that share a unique DNA binding motif, the DM domain. DMRTs regulate development in a broad variety of metazoans and they appear to have controlled sexual differentiation for hundreds of millions of years. In mice, starting during embryonic development, three Dmrt genes act sequentially to help establish and maintain spermatogenesis. Dmrt1 has notably diverse functions that include repressing pluripotency genes and promoting mitotic arrest in embryonic germ cells, reactivating prospermatogonia perinatally, establishing and maintaining spermatogonial stem cells (SSCs), promoting spermatogonial differentiation, and controlling the mitosis/meiosis switch...

The hot deformation behavior of a high carbon carbide-free bainitic steel was studied through isothermal compression tests that were performed on a Gleeble-1500D thermal mechanical simulator at temperatures of 1223-1423 K and strain rates of 0.01-5 s(-1). The flow behavior, constitutive equations, dynamic recrystallization (DRX) characteristics, and processing map were respectively analyzed in detail. It is found that the flow stress increases with increasing the strain rate and decreases with increasing the temperature, and the single-peak DRX can be easily observed at high temperatures and/or low strain rates...

Early childhood marks a time of dynamic development within language and cognitive domains. Specifically, a body of research focuses on the development of language as related to executive functions, which are foundational cognitive skills that relate to both academic achievement and social-emotional development during early childhood and beyond. Although there is evidence to support the relationship between language and executive functions, existing studies focus mostly on vocabulary and fail to examine other components of language such as syntax and language learning skills...